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Immunotherapy and target therapy have revolutionized treatment of stage III/IV melanoma. Both treatments show a favorable toxicity profile even if cutaneous adverse events (AEs) are frequent (30%-40% of cases). This is a retrospective single center cohort study that included patients with stage IV or inoperable stage III metastatic melanoma (AJCC 8th) who received BRAFi + MEKi therapy or immunotherapy with Checkpoint inhibitors. All cutaneous AEs were ascertained by a dermatologist based on clinical and histological findings. The primary outcome was to provide a detailed clinical dermatological classification of cutaneous adverse events and an evaluation of the incidence of skin toxicity in the two arms of therapy (immunotherapy and target therapy). A total of 286 patients with stages III-IV metastatic melanoma were included: 146 received immunotherapy and 140 target therapy. In the immunotherapy cohort, 63 (43.1%) cutaneous reactions were observed while 33 skin reactions (23.6%) were identified in patients treated with target therapy. All the skin toxicities observed were grade I, excepted four cases: an erythema multiforme-like eruption, a grade III psoriasis and two grade III maculopapular rashes. Immunotherapy in older age resulted statistically related to skin toxicities (p = 0.011), meanly in metastatic setting (p = 0.011). Cumulative incidence of skin toxicities was 65.63% in immunotherapy cohort (p = 0.001). Also multivariate logistic regression shows a significant association between skin adverse events and immunotherapy (odds ratio [OR] = 0.50; 95% confidence interval [CI]: 0.29-0.85, p: 0.01) and between cutaneous AEs and metastatic setting (OR = 1.97; 95% CI: 1.04-3.74, p: 0.04). We have also shown that as the age of initiation of therapy increases the probability of developing skin toxicity grows. However, stratifying by type of therapies the effect of age persists only in immunotherapy (OD: 1.04; CI: 1.01-1.06; p: 0.04) while for target therapy age does not affect the onset of skin toxicity (OD 1.01; CI 0.98-1.04; p = 0.42). No differences were shown between patients on target therapy and immunotherapy regarding gender. Patients were also evaluated regarding concomitant therapies and seems that Levotyroxine may be involved in AEs during immunotherapy treatment. More studies are needed to deepen this aspect, also considering the medical history and diverse drug associations. Cutaneous adverse events are characterized by heterogeneous manifestations, are more often seen in patients on immunotherapy and dermatologists can play a crucial role in multidisciplinary care., (© 2022 The Authors. Dermatologic Therapy published by Wiley Periodicals LLC.)

Anorectal malignant melanoma (AMM) is a rare malignant tumor. Surgery remains the gold standard but new adjuvant treatments to allow local sphincter-saving are warranted. Electrochemotherapy (ECT) is an alternative to surgery in selected cohorts of patients. To evaluate safety and efficacy of ECT in a retrospective series of patients with primary or recurrent AMM in terms of local disease control, local progression free and overall survival. Seven primary and one recurrent AMM underwent ECT. Patients were followed at 1 and 2 months and at the longest available follow-up with clinical examination and/or ultrasound. One month after ECT 6/8 (75%) patients showed complete response, 1/8 partial response (12.5%) and 1/8 stable disease (12.5%), confirmed at 2 months. Bleeding stopped in all patients, and pain was absent or mild/moderate in all patients. No serious adverse events were observed. At 1 year of follow-up seven out of eight patients were alive (87.5%), four were disease-free and three were alive with disease. At the longest available follow-up (mean 4.9 ± 2.0 years) five out of eight (62.5%) of patients were still alive. Our study showed that ECT is well tolerated and effective in the treatment of patients with anal melanoma with good local control of disease., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Electrochemotherapy (ECT) is currently used to treat unresectable superficial tumours of different histotypes through the combination of cytotoxic chemotherapy and local application of electric pulses. In 2006, a collaborative project defined the ESOPE (European Standard Operating Procedures of Electrochemotherapy) guidelines to standardize the procedure. The International Network for Sharing Practices of Electrochemotherapy (InspECT) aims to refine the ESOPE and improve clinical practice. Limiting patient exposure to systemic chemotherapy would be advisable to ameliorate ECT safety profile., Objective: The aim of this study was to evaluate the efficacy and toxicity of ECT with reduced chemotherapy dosages., Methods: In a retrospective analysis of a prospectively maintained database (InspECT registry), we evaluated the outcome of patients who received ECT with reduced dosages of bleomycin (7500, 10 000 or 13 500 IU/m 2 , instead of the standard dose of 15 000 IU/m 2 ). Tumour response in melanoma patients was compared with melanoma patients of the InspECT registry who received the standard dose of bleomycin., Results: We identified 57 patients with 147 tumours (melanoma, 38.6%; squamous cell carcinoma, 22.8%; basal cell carcinoma, 17.5%; breast cancer 7%; Kaposi sarcoma 7%; other histotypes, 7.1%). Per-tumour complete response (CR) rate at 60 days was 70.1% (partial, 16.3%); per-patient CR was 57.9% (partial, 21.1%). Local pain was the most frequently reported side-effect (n = 22 patients [39%]), mostly mild; two patients experienced flu-like symptoms, one patient nausea. We observed the same CR rate (55%) in patients with melanoma treated by reduced or conventional bleomycin dosages (P = 1.00)., Conclusions: Electrochemotherapy performed with reduced bleomycin dosages could be as effective as with currently recommended dose. Patients with impaired renal function or candidate to multiple ECT cycles could benefit from a reduced dose protocol. Our findings need prospective confirmation before being adopted in clinical practice., (© 2017 European Academy of Dermatology and Venereology.)

The prognosis of stage IV metastatic melanoma is poor. An overall 1-year survival of 25.5% and a median survival of 6.2 months were reported without any significant improvement during the last 30 years before the introduction of new drugs (immune checkpoint inhibitors and targeted therapies) which completely modified the therapeutic approach and induced an overwhelming improvement on the survival rates of these patients. This review will analyze the therapeutic tools available for the treatment of patients with metastatic melanoma, including adjuvant interferon and locoregional therapies (surgery, radiotherapy and electrochemotherapy) and will mainly focus on the presentation of results obtained by the new treatments (checkpoint inhibitors and targeted therapies).

Background: (ECT) is an effective local treatment for cutaneous metastasis. Treatment involves the administration of chemotherapeutic drugs followed by delivery of electrical pulses to the tumour., Objectives: To investigate the effectiveness of ECT in cutaneous metastases of melanoma and to identify factors that affect (beneficially or adversely) the outcome., Methods: Thirteen cancer centres in the International Network for Sharing Practices on Electrochemotherapy consecutively and prospectively uploaded data to a common database. ECT consisted of intratumoral or intravenous injection of bleomycin, followed by application of electric pulses under local or general anaesthesia., Results: In total, 151 patients with metastatic melanoma were identified from the database, 114 of whom had follow-up data of 60 days or more. Eighty-four of these patients (74%) experienced an overall response (OR = complete response + partial response). Overall, 394 lesions were treated, of which 306 (78%) showed OR, with 229 showing complete response (58%). In multivariate analysis, factors positively associated with overall response were coverage of deep margins, absence of visceral metastases, presence of lymphoedema and treatment of nonirradiated areas. Factors significantly associated with complete response to ECT treatment were coverage of deep margins, previous irradiation of the treated area and tumour size (< 3 cm). One-year overall survival in this cohort of patients was 67% (95% confidence interval 57-77%), while melanoma-specific survival was 74% (95% confidence interval 64-84%). No serious adverse events were reported, and the treatment was in general very well tolerated., Conclusions: ECT is a highly effective local treatment for melanoma metastases in the skin, with no severe adverse effects noted in this study. In the presence of certain clinical factors, ECT may be considered for local tumour control as an alternative to established local treatments, or as an adjunct to systemic treatments., (© 2017 British Association of Dermatologists.)

Cancer survival rates are lower in Eastern Europe. To describe, based on a single-centre database in northern Italy, clinical, histopathological, and prognostic features of melanoma in a migrant population from Eastern Europe., Materials & Methods: We retrospectively analysed data from 18,190 consecutive foreign patients who visited our institution, with 49 cases of melanoma from Eastern Europe. The control group was represented by 1,003 Italian melanoma patients diagnosed and followed at our centre during the same time period. Patients from Eastern Europe were mainly females with lower median age, without significant differences regarding primary melanoma site, relative to the control group. Diagnosis was made at the place of birth in 30.6% and in our centre for the remainder. Median Breslow thickness was greater (p = 0.0178), and aggressive histotypes (p = 0.0017) and ulcerated melanomas (p = 0.002) were significantly over-represented, particularly when diagnosed in the patients' native country. Disease was more advanced at diagnosis (p = 0.0001), regardless of the place of initial diagnosis (51% had a progressive disease within one year which rose to 80% if diagnosed before admission to our centre), and the percentage of patients who died within one year was significantly higher (p = 0.022), relative to the control group. Our study shows a poor prognosis for melanoma patients diagnosed in Eastern Europe. Moreover, for migrant populations moving from Eastern to Western European countries, financial difficulties, poor social integration, and language barriers, with consequent late access to healthcare facilities, may account for a worse prognosis.

Background: Targeted therapies have recently changed the approach to advanced melanoma. RAF inhibitors represent the emerging standard of care for metastatic BRAF mutated melanomas. Cutaneous reactions are the most common side effects during vemurafenib treatment, and affect the quality of life. The aim of this study was to provide some practical advices to manage the drug related cutaneous reactions., Methods: A cohort of BRAF-mutated metastatic melanoma patients treated at our institution included 20 female and 21 male patients; median age was 56 years (32-87 years). All patients were treated at a dose of 960 mg b.i.d. orally., Results: After a median treatment duration of 7 months (range 0.5-25.2), 29/39 patients (74.4%) developed cutaneous toxicities. We identified 22 cases of maculo-papular rash (56%) and 18 of warts (46%); in a total of 10 cases we observed alterations of keratinization (25.6%), while 6 of our patients presented photosensitivity (15 %). Six patients developed keratoacanthomas; no second melanomas were observed., Conclusions: Skin involvement during vemurafenib treatment is frequent but in the majority of cases cutaneous side effects are self-limiting and easy to manage. Moreover, sun protection is mandatory in vemurafenib treated patients, and should be started together with BRAF inhibitor in order to minimize the impact of photosensitivity on quality of life.

Background: Electrochemotherapy (ECT) effectively controls skin metastases from cutaneous melanoma. Objectives: This study aimed to evaluate health‐related quality of life (HRQoL) in melanoma patients pre−/post‐ECT and its effect on treatment outcome. Methods: The analysis included prospective data from the International Network for Sharing Practices of ECT register. Following the Standard Operating Procedures, patients received intravenous or intratumoural bleomycin (15 000 IU/m2; 1000 IU mL/cm3) followed by 100‐microsecond, 1000‐V/cm electric pulses. Endpoints included response (RECIST v3.0), local progression‐free survival (LPFS), toxicity (CTCAE v5.0), and patient‐reported HRQoL at baseline, one, two, four, and 10 months (EuroQol [EQ‐5D‐3L], including 5‐item utility score [EQ‐5D] and visual analogue scale for self‐reported health state [EQ‐VAS]). Comparisons within/between subgroups were made for statistical and minimal important differences (MID). HRQoL scores and clinical covariates were analysed to identify predictors of response in multivariate analysis. Results: Median tumour size was 2 cm. Complete response rate, G3 toxicity, and one‐year LPFS in 378 patients (76% of the melanoma cohort) were 47%, 5%, and 78%, respectively. At baseline, age‐paired HRQoL did not differ from the general European population. Following ECT, both EQ‐5D and EQ‐VAS scores remained within MID boundaries, particularly among complete responders. A subanalysis of the EQ‐5D items revealed a statistically significant deterioration in pain/discomfort and mobility (restored within 4 months), and self‐care and usual activities (throughout the follow‐up) domains. Concomitant checkpoint inhibition correlated with better EQ‐5D and EQ‐VAS trajectories. Baseline EQ‐5D was the exclusive independent predictor for complete response (RR 14.76, P = 0.001). Conclusions: HRQoL of ECT melanoma patients parallels the general population and is preserved in complete responders. Transient deterioration in pain/discomfort and mobility and persistent decline in self‐care and usual activities may warrant targeted support interventions. Combination with checkpoint inhibitors is associated with better QoL outcomes. Baseline HRQoL provides predictive information, which can help identify patients most likely to respond. [ABSTRACT FROM AUTHOR]